Alternate splicing of death receptor 3 (DR3) results in 8 soluble receptors . The hypothesis is that soluble DR3 (sDR3) variants are able to sequester its cognate ligand ,VEGI. This will be a novel mechanism of regulating VEGI activity. VEGI has anti-cancer activity and overexpresion of sDR3 may be mechanism of avoiding the anti-angiogenic properties of VEGI. Leukemia cells have the ability to switch there soluble DR3 isoforms to the full length isoform and the role of VEGI is unknown in these cells. If it is found that VEGI can induce apoptosis in leukemia cells after isform switching this will be provide new therapeutic approach for the use of VEGI in treatment of leukemia. Aim 1. Determine if recombinant sDR3 can inhibit VEGI activity in endothelial cells. Endothelial cells will be co-treated with recombinant sDR3 and recombinant VEGI in order to show that sDR3 can inhibit VEGI activation of NF-kappab and caspase-3. Aim 2. Determine if isoform switching in leukemia cells results in an increase in VEGI activity. Leukemia cells will be induced to switch from their soluble DR3 variants to the membrane bound variant in order to show an increase in VEGI activation of NF-kappab and caspase-3.